Haematophagous insects and certain other blood-feeding arthropods are ubiquitous ectoparasites of animals, including humans. In so doing, blood-feeding ectoparasitic arthropods constitute a major source of annoyance to humans and other animals, and are vectors of many microbial diseases, as well as those caused by viruses and virus-like disease agents (Harwood and James 1979).
Blood-feeding arthropods that annoy man and animals through their biting and feeding activity, and often vector disease-causing pathogens, comprise members of numerous insect taxa, including, but not limited to: flies in the Families Culicidae, Tabanidae, Psychodidae, Simuliidae, Muscidae and Ceratopgonidae (Order Diptera), bugs in the Families Cimicidae and Reduviidae (Order Hemiptera), lice in the Orders Mallophaga and Anoplura, and fleas in the Order Siphonaptera, as well as non-insectan arthropods, particularly ticks and mites in the Order Acari (also known as Acarina).
An example of a significant annoyance to humans and a major vector of disease-causing pathogens is the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae), an exceptionally resilient blood-feeding species that breeds in any small container of water (Malavige et al. 2004). Adults are highly domesticated, typically resting indoors in dwellings, thus optimizing their opportunity to feed and vector pathogens that cause diseases such as yellow fever and dengue fever (Mackenzie et al. 2004; Malavige et al. 2004; Hill et al. 2005). Annually, 7.2 million humans become infected with yellow fever, and >30,000 die from the disease. Moreover, 50-100 million humans are infected with dengue fever (500,000 with its hemmorhagic form), resulting in approximately 24,000 deaths annually (Zanotto et al. 1996; Mairuhu et al. 2004). Other species of Aedes, as well as mosquitoes in other genera, particularly Anopheles and Culex, are also significant annoyance agents and vectors of disease-causing pathogens.
The most effective protection against mosquitoes and other ectoparasitic arthropods, is to repel them from, or deter their landing and feeding on, potential hosts. Until recently, the most efficacious known “repellent” was N,N-diethyl-m-toluamide (DEET) (Fradin and Day 2002). There are concerns associated with N,N-diethyl-m-toluamide. It is a solvent for some plastics, paints, varnishes and synthetic fabrics (Trigg 1996; Badolo et al. 2004; Miot et al. 2004). When used alone it may attract rather than repel A. aegypti. Finally, products exceeding 30% N,N-diethyl-m-toluamide are not recommended for protection of children (Pest Management Regulatory Agency 2002). Thus, there is a strong need for alternatives to N,N-diethyl-m-toluamide.
Research has led to several alternative repellents and deterrents to date, some of them with efficacy equal to that of N,N-diethyl-m-toluamide (Barnard and Xue 2004). Many of these are natural compositions, and include essential oils from plants (cedar, rosemary, eucalyptus, andiroba, catnip, thyme, neem, clove, soybean) and grease or oils from animals. Active ingredients in some of these oils have been isolated and formulated in commercial products. OFF!® botanicals, for example, contain p-menthane-3,8-diol from lemon eucalyptus, Eucalyptus maculata citriodon (Beldock et al. 1997; Carroll and Loye 2006) as the active ingredient. Other new repellents for mosquitoes and other arthropods that are found in natural sources include: 2-undecanone (methyl nonyl ketone) from tomato plants (Roe 2002, 2004, 2007; Roe et al. 2006); tetrahydronootkatone (1,4,4a,5,6,7,8,10-octahydro-6-isopropyl-4,4a-dimethyl-2(1H)-naphthalenone) and 1,10-dihydronootkatone (1,4,4a,5,6,7,8,10-octahydro-6-isopropenyl-4,4a-dimethyl-2(1H)-naphthalenone) from yellow cedar (Zhu et al. 2005); and callicarpenal (13,14,15,16-tetranor-3-cleroden-12-al) and intermedeol [(4S,5S,7R,10S)-eudesm-11-en-4-ol] from American beautyberry (Cantrell et al. 2005, 2006; Carroll et al. 2007).
Most recently, Gries et al. (2009) report analyses of odorants in garlic essential oil with the objectives to (i) understand the moiety(ies) of molecules that convey offensive smell and insect repellency and (ii) engineer odorless compounds with greater repellency than their natural counterparts. The invention by Gries et al. (2009) relates to compounds that incorporate one or more allyl sulfide, allyl disulfide, and/or allyl polysulfide moieties, and one or more hydroxyl groups, and are used to repel or deter landing and feeding of mosquitoes on humans. 8-Allylsulfanyloctan-1-ol was the key compound which by itself or in combination with an adjuvant was more effective than DEET in deterring biting by the mosquitoes Anopheles gambiae, Culex quinquefasciatus, and Aedes aegypti. 